BPL-003's Phase 3 dose rests on a 46-patient Phase 2b arm, while new trials test 4 mg, 8 mg and placebo

BPL-003's Phase 2b trial met its primary endpoint, with 12 mg improving day-29 MADRS scores by 5.3 points more than a 0.3 mg comparator. However, the 8 mg dose selected for Phase 3 was tested in only 46 patients after a recruitment-related amendment changed randomization, leaving the trial too imprecise to establish similar efficacy to 12 mg. Both active doses produced comparable improvements, while 8 mg generally caused less nausea, anxiety, panic and blood pressure elevation. The low-dose comparator also improved substantially, and its subperceptual design could not fully prevent functional unblinding. The paper's claim that most patients were ready for discharge within two hours describes an assessment, not actual discharge, since the protocol required at least four hours of observation. Phase 3 will test 8 mg and 4 mg against placebo in larger randomized trials, with results expected around early 2029.